This proposal is designed to investigate viral antigen recognition by HLA-restricted T lymphocytes and the pathways of viral antigen presentation to T lymphocytes restricted by HLA class I and class II locus products. It is an extension into the human of our ongoing study of immune recognition of the type A influenza viruses. Over the last several years fundamental observations in the field of immunology have opened up new areas of investigation into the structure of antigenic moieties recognized by the antigen receptor on T lymphocytes and the nature of the interaction of antigen and major histocompatibility complex (MHC) gene products. Recently, a major emphasis of our research program has been the analysis of the mechanism of antigen presentation to T lymphocytes where evidence from ours and other laboratories points to major differences in the pathways of antigen presentation to T lymphocytes of different subsets. The examination of these pathways of antigen presentation as well as the definition of antigenic sites on influenza viral polypeptides is the focus of the proposed research. Our class II restricted human T lymphocytes: 1) to characterize influenza virus antigenic moieties which serve as antigenic sites recognized by human T lymphocytes; 2) to examine the antigen presentation events leading to the processing and recognition of influenza polypeptides by human T lymphocytes. Eukaryotic expression vectors will be employed to express influenza genes or fragments of genes in order to identify antigenic sites. Synthetic peptides which mimic these sites will be used to define critical amino acids necessary for binding to class I or class II MHC gene products and/or interaction with T lymphocyte antigen receptors. This investigation should provide basic information on the characteristics of antigenic moieties which are recognized by T lymphocytes directed to this important human pathogen. In addition, these studies should help to elucidate the similarities and differences in the mechanism of antigen presentation to "helper" and "killer" T lymphocytes and thereby provide an important framework for future vaccine design.